Zic family pp 269-299 | Cite as

ZIC2 in Holoprosencephaly

  • Kristen S. Barratt
  • Ruth M. Arkell
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1046)


The ZIC2 transcription factor is one of the most commonly mutated genes in Holoprosencephaly (HPE) probands. HPE is a severe congenital defect of forebrain development which occurs when the cerebral hemispheres fail to separate during the early stages of organogenesis and is typically associated with mispatterning of the embryonic midline. Recent study of genotype-phenotype correlations in HPE cases has defined distinctive features of ZIC2-associated HPE presentation and genetics, revealing that ZIC2 mutation does not produce the craniofacial abnormalities generally thought to characterise HPE but leads to a range of non-forebrain phenotypes. Furthermore, the studies confirm the extent of ZIC2 allelic heterogeneity and that pathogenic variants of ZIC2 are associated with both classic and middle interhemispheric variant (MIHV) HPE which arise from defective ventral and dorsal forebrain patterning, respectively. An allelic series of mouse mutants has helped to delineate the cellular and molecular mechanisms by which one gene leads to defects in these related but distinct embryological processes.


Zic2 Holoprosencephaly Syntelencephaly Prechordal plate Telencephalon Dorsal-ventral pattern Nodal Hedgehog Wnt BMP 


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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Early Mammalian Development Laboratory, John Curtin School of Medical ResearchThe Australian National UniversityCanberraAustralia

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